Active ingredients with low solubility very often have the problem of insufficient bioavailability. The solution generally adopted for this problem is increasing the solubility of these active ingredients. Examples of this are using a dissolving intermediary via solubilization, the formation of inclusion compounds (e.g. with cyclodextrines) and the use of solvent mixtures (K. H. Bauer, K.-H. Frömming, C. Führer, Pharmazeutische Technologie, Georg Thieme Verlag Stuttgart, 1991). For many active ingredients, however, this does not lead to a sufficient increase in solubility, especially if active ingredients are simultaneously difficult to dissolve in aqueous media and in organic media. Here, for example, solvent mixtures are ruled out as a solution to the problem. Alternatively active ingredients which are only slightly soluble in water can be dissolved in oils, an O/W emulsion can be produced and this can then be administered orally or parenterally, usually intravenously. Very many active ingredients, especially active ingredients which are at the same time only slightly soluble in aqueous and organic media, are however not sufficiently soluble in oils. Not sufficiently means that, because the solubility is too low, the volume of emulsion to be administered for the necessary dose is too large.
Active ingredients that are only slightly soluble in water and in oils, such as Amphotericin B, can however be incorporated into emulsions (Seki et al. U.S. Pat. No. 5,534,502). To achieve this, however, additional organic solvents must be used. These solvents must then be removed again in intermediate stages of the emulsion production or from the product (Davis, Washington, EP 0 296 845 A1) in which however a certain residual solvent content remains in the product. In addition, this production process takes a great deal of time, and is cost-intensive, so that practically no products based on this technology are represented on the market. An alternative method is the intercalation of such substances as Amphotericin B into the phospholipid double membrane of liposomes; a commercial product is for example AmBisome® (Janknegt et al., Liposomal and lipid formulations of amphotericin B., Clin. Pharmacokinet., 23,279–291 [1992]). A disadvantage of this, however, is the very expensive production process, which means that, as a rule, it is used only in emergencies, when another treatment does not achieve the aim, or only for patients who are financially in a position to pay for the treatment. Thus there is a clear need for an economical formulation, which is at the same time as simple as possible to produce, unlike liposomes is stable in storage, does not require lyophilization and does not contain residual solvents.
There is therefore need for a dispersion which contains an active ingredient, which hitherto could only be dissolved slightly, with difficulty or not at all, that is dissolved in a quantity hitherto not possible. There is also a need for a dispersion which avoids the disadvantages described above, such as the use of additional organic solvents hitherto necessary to form a formulation.